Customized MethylC-Capture Sequencing to Evaluate Variation in the Human Sperm DNA Methylome Representative of Altered Folate Metabolism

Environmental Health Perspectives
D ChanJacquetta M Trasler

Abstract

The sperm DNA methylation landscape is unique and critical for offspring health. If gamete-derived DNA methylation escapes reprograming in early embryos, epigenetic defects in sperm may be transmitted to the next generation. Current techniques to assess sperm DNA methylation show bias toward CpG-dense regions and do not target areas of dynamic methylation, those predicted to be environmentally sensitive and tunable regulatory elements. Our goal was to assess variation in human sperm DNA methylation and design a targeted capture panel to interrogate the human sperm methylome. To characterize variation in sperm DNA methylation, we performed whole genome bisulfite sequencing (WGBS) on an equimolar pool of sperm DNA from a wide cross section of 30 men varying in age, fertility status, methylenetetrahydrofolate reductase (MTHFR) genotype, and exposures. With our targeted capture panel, in individual samples, we examined the effect of MTHFR genotype ([Formula: see text] 677CC, [Formula: see text] 677TT), as well as high-dose folic acid supplementation ([Formula: see text], per genotype, before and after supplementation). Through WGBS we discovered nearly 1 million CpGs possessing intermediate methylation levels (20-80%), termed dynam...Continue Reading

References

Jun 27, 2007·International Journal of Epidemiology·L H LumeyEzra S Susser
Nov 7, 2008·Methods in Molecular Biology·Emelyne DejeuxJörg Tost
May 20, 2009·Bioinformatics·Heng Li, Richard Durbin
May 28, 2009·European Journal of Human Genetics : EJHG·Hisato KobayashiTakahiro Arima
Jun 16, 2009·Nature·Saher Sue HammoudBradley R Cairns
Oct 2, 2009·The International Journal of Neuropsychopharmacology·Yael Chertkow-DeutsherDorit Ben-Shachar
Nov 3, 2009·International Journal of Andrology·A PoplinskiJ Gromoll
Nov 20, 2009·The American Journal of Clinical Nutrition·Regan L BaileyMary Frances Picciano
Nov 26, 2009·Human Reproduction Update·Trevor G CooperKirsten M Vogelsong
May 18, 2010·Nature Structural & Molecular Biology·Urszula BrykczynskaAntoine H F M Peters
Dec 15, 2010·PLoS Computational Biology·Eugene V DavydovSerafim Batzoglou
Apr 16, 2011·Bioinformatics·Felix Krueger, Simon R Andrews
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Jul 13, 2012·Genome Biology·Yaping LiuBenjamin P Berman
Aug 9, 2012·Current Protocols in Molecular Biology·Michelle D JohnsonTimothy J Aitman
Aug 9, 2013·Nature·Michael J ZillerAlexander Meissner
Sep 7, 2013·Nature Protocols·Michael J BoothShankar Balasubramanian
Mar 25, 2014·American Journal of Physiology. Heart and Circulatory Physiology·Adam J Watkins, Kevin D Sinclair
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Oct 23, 2014·Bioinformatics·Neo Christopher Chung, John D Storey
Nov 29, 2014·Genetics Research International·Elif Funda SenerYusuf Ozkul
Dec 3, 2014·European Journal of Medical Genetics·Siaw-Cheok Liew, Esha Das Gupta
May 26, 2015·Cell·Sofia GkountelaAmander T Clark
Aug 13, 2015·Seminars in Cell & Developmental Biology·Lundi LyJacquetta M Trasler
Sep 12, 2015·Fertility and Sterility·Kenneth I AstonDouglas T Carrell
Oct 11, 2015·Fertility and Sterility·Timothy G JenkinsDouglas T Carrell
Dec 17, 2015·Cell Metabolism·Ida DonkinRomain Barrès
Dec 17, 2016·Epigenetics & Chromatin·Michael J ZillerAlexander Meissner

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Datasets Mentioned

BETA
EGAS00001003617

Methods Mentioned

BETA
WGBS
MCC-Seq
Genotyping
PCR
electrophoresis
RRBS
Methylation
WGBS-Pool
Methyl
targeted mutation

Software Mentioned

Trimmomatic
R function glm
R package q - values
GraphPad Prism
intersectBed
Picard
WGBS
Prev
HOMER
Pool

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